This research is designed to investigate interactions betwween metals and several direct-acting mutagens. The approach is along two lines. the first is to develop further the fluctuation assay, using S. typhimurium and E. coli, for the detection and characterization of mutagenic interactions. The second is to apply various modifications of the fluctuation protocol, different tester strains of the bacteria and several in vitro assays for DNS repair to the study of mechanisms underlying interactions observed. The objective is to use the fluctuation test to compare the actions of metal and non-metal mutagens alone and in combination. The data can then be analyzed statistically for greater-than-additive, additive and less-than-additive interactions. Greater-than-additive effects would indicate a synergism between the metal and the non-metal mutagens alone and in combination. The data can then be analyzed statistically for greater-than-additive effects would indicate a synergism between the metal and the non-metal tested. Such an action would probably reflect the ability of the metal to enhance the mutagenic consequences to the bacteria of the DNA damage done by the non-metal. Synergistic interactions would have potentially important consequences for persons exposed both to metals and other environmental mutagens. This type of interaction, ad exa=emplified by the synergism between chromium (VI) and azide, would be further investigated by using tester strains of bacteria deficient in enzyme and/or repair functions involved in the replication and maintenance of DNA. The absence of a synbergistic interaction in a deficient strain would implicate the deficient function in the mechanism of metal action. This effect of the metal could then be confirmed in specific in vitro assays for different types of DNA repair. Results are expected to be valuable in the assessment of the potential of metals to interact with mutagens and in the refinement of current hypothesis for mechanism of metal genotoxicity.